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Polymer sequencing by molecular machines - new publication by Andrew Round

A microscope that allows scientists to manipulate individual molecules may in the future be used to sequence complex sugar-containing molecules that are critical in the development of new drugs, following new work by Dr. Andrew Round in the School of Pharmacy, published in Nanoscale.

Unlike DNA and proteins it is currently impossible to sequence long chains of sugars (called polysaccharides) that perform critical roles in many physiological processes. Dr. Round, in collaboration with Profs Gudmund Skjåk-Bræk and Bjørn Stokke at NTNU, Trondheim, Norway, has shown that a simple model can be used to predict whether an atomic force microscope (AFM) can distinguish between different parts of proteins and carbohydrate chains. The microscope uses a ring molecule called cyclodextrin that slides along the chain molecule, reading the force it requires to slide the ring along the chain. The paper shows that we only need to know two things about each part of the chain – its size and its hydrophobicity (whether it prefers to be in water or in oil) – to predict the force required to slide the ring molecule over it.

The results reveal that the method can map the pattern of specific sequences within the protein or carbohydrate chain. These patterns can determine how effective a molecule is at disrupting disease processes in cancer and other ailments.

Read the publication here.

Sliding contact force spectroscopy works by picking up a ring molecule and sliding it along a polymer chain. It can distinguish between different parts of the chain on the basis of their size and hydrophobicity.